Matrix stiffness-mediated effects on stemness characteristics occurring in HCC cells.

Area of Science:

• Biomedical Engineering
• Cancer Biology
• Cell Biology

Background:

• Extracellular matrix stiffness significantly influences cancer cell behaviors.
• The impact of matrix stiffness on cancer stemness in hepatocellular carcinoma (HCC) remains largely unknown.

Purpose of the Study:

• To investigate the role of matrix stiffness in regulating stemness characteristics of HCC cells.
• To elucidate the underlying molecular signaling pathways involved.

Main Methods:

• Culturing HCC cells on substrates with varying stiffness.
• Assessing stemness markers (CD133, EpCAM, Nanog, SOX2) and self-renewal ability.
• Analyzing signaling pathway components (integrin β1, Akt, mTOR, 4E-BP) via Western blotting and inhibitor treatments.

Main Results:

• Increased matrix stiffness promoted stemness markers, self-renewal, and oxaliplatin resistance in HCC cells.
• Higher stiffness upregulated phosphorylation of Akt and mTOR, and expression of p-4E-BP and SOX2.
• Integrin β1 knockdown and mTOR inhibition attenuated stiffness-induced stemness and reversed signaling pathway activation.

Conclusions:

• Matrix stiffness promotes HCC stemness through the integrin β1/Akt/mTOR/SOX2 signaling pathway.
• This study reveals a novel regulatory pathway for stemness in HCC cells.
• Targeting this pathway may offer new therapeutic strategies for HCC.